Intestinal Glucagon-like Peptide-1 (GLP-1) and the Physiological Role in Eating in Humans

The aim is to further establish a physiological role for GLP-1 as an endogenous satiety signal by examining the effect of the specific GLP-1 receptor antagonist exendin (9-39) on appetite and food intake in healthy male subjects.

Study Overview

• Status: Completed
• Conditions: Appetite and General Nutritional Disorders
• Intervention / Treatment: Dietary supplement: Saline; Dietary supplement: Saline; Drug: Exendin 9-39; Drug: Exendin(9-39) plus ID nutrient

Detailed Description

Understanding the exact mechanisms by which GLP-1 inhibits eating can be crucial in order to convert its anorectic action into useful, safe and effective drugs. So far, it is however not clear to what extent GLP-1 is a hormonal regulator of eating or whether the observed effects are rather a pharmacological phenomenon. By applying classical algorithms from endocrinology several criteria must be fulfilled before a hormone can be considered an endogenous physiological satiety signal. One is that exogenous administration of a selective antagonist should prevent the eating-inhibitory effect of GLP-1. At present, cholecystokinin (CCK) is the only peptide in humans identified to fit these criteria. For intestinal GLP-1, it has not been investigated whether a specific GLP-1 receptor antagonist can block the eating-inhibitory effect in humans. The availability of a specific GLP-1 receptor antagonist, exendin (9-39), now makes it possible to further investigate this pathway. Exendin (9-39), is a powerful tool available for human use to characterize of endogenous GLP-1 as a physiological regulator of different biological functions. The molecule has been used to document that endogenous GLP-1 is an important incretin hormone and a regulator of antro-pyloro-duodenal motility. The role of endogenous GLP-1 in regulating food intake and appetite has, however, not been investigated before.

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Switzerland
  • Basel, Switzerland
    • University Hospital Basel, Phase 1 Research Unit

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

1. Healthy male subject with a BMI of 19-25 m2/kg
2. Stable body weight for at least three months
3. Normal eating habits
4. Age between 18 and 45 years
5. Sufficient understanding of the German language
6. Subjects understand the procedures and the risks associated with the study
7. Participants must be willing to adhere to the protocol and sign the consent form

Exclusion Criteria:

1. Participation in another clinical trial (currently or within the last 30 days)
2. Smoking
3. Substance abuse
4. Regular intake of medications (except for oral contraceptives)
5. Chronic or acute medical condition including clinically relevant abnormality in physical exam or laboratory values
6. History of gastrointestinal disorders
7. Food allergies

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: iv saline, intraduodenal saline; intravenous infusion of saline plus intraduodenal administration of saline	Dietary supplement: Saline; Intravenous saline infusion and intraduodenal administration of saline via feeding tube; Dietary supplement: Saline; IV saline infusion and intraduodenal administration of nutrients
Active Comparator: IV exendin(9-39) plus intraduodenal (ID) saline; intravenous infusion of exendin(9-39) plus intraduodenal administration of saline	Drug: Exendin 9-39; IV exendin(9-39) infusion and intraduodenal administration of saline via feeding tube
Placebo Comparator: IV saline, intraduodenal nutrient; intravenous infusion of saline plus intraduodenal administration of nutrient	Dietary supplement: Saline; Intravenous saline infusion and intraduodenal administration of saline via feeding tube; Dietary supplement: Saline; IV saline infusion and intraduodenal administration of nutrients
Active Comparator: Exendin(9-39) plus ID nutrient; Exendin(9-39) as intravenous infusion plus intraduodenal nutrient administration	Drug: Exendin(9-39) plus ID nutrient; Exendin(9-39) as intravenous infusion plus intraduodenal nutrient administration

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Effect of exendin(9-39)on total calorie intake	60 min test meal
Effect of exendin(9-39) on total fluid intake	60 min test meal
Effect of exendin(9-39)on meal duration during an ad libitum test meal.	60 min test meal

Secondary Outcome Measures

Outcome Measure	Time Frame
Effect of exendin(9-39)on plasma concentration of glucose	4 hours blood sampling
Effect of exendin(9-39)on plasma concentration of insulin.	4 hours blood sampling
Effect of exendin(9-39)on plasma concentration of glucagon.	4 hours blood sampling
Effect of exendin(9-39)on plasma concentration of GLP-1.	4 hours blood sampling
Effect of exendin(9-39)on plasma concentration of peptide tyrosine tyrosine (PYY).	4 hours blood sampling
Effect of exendin(9-39)on plasma concentration of CCK.	4 hours blood sampling
Effect of exendin(9-39)on plasma concentration of ghrelin.	4 hours blood sampling

Collaborators and Investigators

• Sponsor: University Hospital, Basel, Switzerland
• Investigators: Principal Investigator: Christoph Beglinger, MD, University Hospital Basel, Phase 1 Research Unit, Basel Switzerland

Publications and helpful links

General Publications

• Steinert RE, Schirra J, Meyer-Gerspach AC, Kienle P, Fischer H, Schulte F, Goeke B, Beglinger C. Effect of glucagon-like peptide-1 receptor antagonism on appetite and food intake in healthy men. Am J Clin Nutr. 2014 Aug;100(2):514-23. doi: 10.3945/ajcn.114.083246. Epub 2014 Jun 25.

Study record dates

Study Major Dates

• Study Start: November 1, 2011
• Primary Completion (Actual): December 1, 2012
• Study Completion (Actual): December 1, 2012

Study Registration Dates

• First Submitted: April 3, 2012
• First Submitted That Met QC Criteria: July 11, 2013
• First Posted (Estimate): July 16, 2013

Study Record Updates

• Last Update Posted (Estimate): July 16, 2013
• Last Update Submitted That Met QC Criteria: July 11, 2013
• Last Verified: July 1, 2013

More Information

Terms related to this study

• Keywords: GLP-1; food intake; satiation peptides
• Additional Relevant MeSH Terms: Nutrition Disorders
• Other Study ID Numbers: EKBB 25/11